Relationships between plasma tryptophan and brain tryptophan, and consequences on CNS serotonin metabolism in the exercising rat

Abstract

The present paper will review the consequences of physical exertion (treadmill running) on CNS serotonin (5-hydroxytryptamine, 5-HT) synthesis and metabolism in the rat with regard to the relationships between plasma and brain tryptophan (TRP), i.e. 5-HT precursor. Trained rats were run for 1 h or 2 h and compared to trained rats that were left to rest during identical periods of time. The results indicate that exercise increases the portion of plasma TRP that is unbound to albumin (free TRP) without affecting that of plasma total (free plus albumin-bound) TRP. Exercise-induced lipolysis was found to be the determinant of the rise in plasma-free TRP inasmuch as free fatty acids displace TRP from its binding to albumin. These changes were associated with minor or no changes in the plasma levels of the amino acids that compete with TRP for entry into the brain. Moreover, the intrinsic kinetics of the transport system that allows TRP (and other neutral amino acids) to enter into the brain were found to be unaffected by exercise. These peripheral modifications were associated with a marked rise in brain TRP which, in turn, led to an increase in 5-HT metabolism. However, the rise in brain 5-HT synthesis and metabolism was found to be associated with a partial inhibition of tryptophan hydroxylase activity, thus rendering a key role for the increase in precursor availability. Indeed, pharmacological experiments led with an inhibitor of 5-HT synthesis revealed a region-dependent alteration in tryptophan hydroxylase activity. Inasmuch as CNS 5-HT is involved in mood regulation, it is important to appreciate the extent to which the above related exercise-induced changes in 5-HT metabolism are involved in the purported psychological benefit of physical exertion.